This proposed Alcohol Research Center is focussed on the genetics of neuroadaptation to ethanol. A program of research and training, and the establishment of a centralized educational resource is proposed. The central research goal of our current program project is to determine the extent to which there were common genetic determinants of different measures of neuroadaptation to ethanol. Genetic mapping techniques brought to fruition early during the course of the current grant allowed provisional identification of the map location of individual genes (Quantitative Trait Loci, or QTLs) affecting behavioral and pharmacological responses to ethanol. One major theme to be carried forward from the initial program period into the proposed center projects is a unique focus on mapping and verification of provisional QTLs relevant for neuroadaptation to ethanol, and development of new genetic animal models (e.g., congenic strains) for studying the effects of verified QTLs. Th ultimate goal of these studies is to identify the specific relevant genes and their functional roles. The second major theme is the use of genetic animal models to explore the neuropharmacological and neuroendocrine mechanisms underlying ethanol responses. Several projects and pilot projects will explore responses related to ethanol's hedonic, anxiolytic, and withdrawal effects. The role of specific candidate genes, in many cases initially identified by QTL mapping, underlying ethanol sensitivity, tolerance and dependence will be explored. The search for additional provisional QTLs for ethanol responses will be advanced, centralized data banks for genetic markers, phenotypic sensitivity scores, and QTLs for ethanol responses will be maintained and used to coordinate Center information management.